Systemic sclerosis (SSc) is a multisystem connective tissue disorder featured by vascular injury as well as fibrosis of the skin and various internal organs with an autoimmune background. Although the pathogenesis of SSc still remains elusive, it is generally accepted that initial vascular injury due to autoimmunity and environmental factors causes structural and functional abnormalities of the vasculature which eventually result in the constitutive activation of fibroblasts and their evolution to myofibroblasts in various organs.
SSc is characterized by structural alteration of the vasculature, which includes destructive vasculopathy, or loss of small vessels and progressive obliterative vasculopathy, thickening of vessel walls and occlusion of arterioles and small arteries. SSc also is characterized by impaired vasculogenesis and angiogenesis.
Impaired function of SSC vasculature includes the altered expression of cell adhesion molecules, endothelial dysfunction, activated endothelial to mesenchymal transition leading to abnormalities of the vasculature and impaired coagulation/thrombosis.
Structural abnormalities of the vasculature in SSc patients are classified into two categories, these being destructive vasculopathy and proliferative obliterative vasculopathy. Destructive vasculopathy is characterized by a progressive loss of small blood vessels, whereas proliferative obliterative vasculopathy is due to excessive proliferation of vascular endothelial and smooth muscle cells leading to the occlusion of arterioles and small arteries. The vascular abnormalities are caused by impaired or abnormal compensatory vasculogenesis, along with angiogenesis, and vascular remodeling, which leads to tissue hypoxia and dermal fibroblast activation, and other features of scleroderma such as digital ulcers, PAH, and scleroderma renal crisis.